Lymphocytes as cell model to study apoptosis in Alzheimer's disease: vulnerability to programmed cell death appears to be altered

Recent evidence indicates that programmed cell death (apoptosis) may contri bute to neuronal death in Alzheimer's disease (AD). In situ data derived fr om post mortem brain tissue indicate that DNA fragmentation which represent s an important and typical apoptotic feature is markedly increased in brain cells of AD patients compared to controls. Furthermore, in vitro studies d emonstrate that the peptide beta-amyloid (A beta) and its fragments induce apoptosis in neuronal cell cultures. One possible mechanism initiating apop tosis could be free radical generation by the peptide leading to oxidative stress. In a wide range of cell types common morphological and molecular ev ents occur during apoptosis and several genes appear to be involved. Partic ularly in lymphocytes, apoptosis plays an important physiological role. Our data demonstrate that similar oxidative stressors induce apoptosis in matu re human lymphoctes as in neurons. In addition, first evidence indicates th at susceptibility to apoptosis is altered in lymphocytes from AD patients c ompared to non-demented controls. Our preliminary findings suggest that cha nges of the individual sensitivity to undergo cellular apoptosis are alread y detectable in lymphocytes from AD patients, probably as a consequence of genetic as well as other risk factors. Therefore, this biochemical marker m ight have the potential for identifying individuals at risk of the diseases .